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Comparative analysis of visual and semi-quantitative assessment of striatal [123I]FP-CIT-SPET binding in Parkinson's disease.

We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.

Aged↗

Haploview: analysis and visualization of LD and haplotype maps.

UNLABELLED: Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface. AVAILABILITY: http://www.broad.mit.edu/mpg/haploview/ CONTACT: jcbarret@broad.mit.edu

Algorithms↗

GObar: a gene ontology based analysis and visualization tool for gene sets.

BACKGROUND: Microarray experiments, as well as other genomic analyses, often result in large gene sets containing up to several hundred genes. The biological significance of such sets of genes is, usually, not readily apparent. Identification of the functions of the genes in the set can help highlight features of interest. The Gene Ontology Consortium 1 has annotated genes in several model organisms using a controlled vocabulary of terms and placed the terms on a Gene Ontology (GO), which comprises three disjoint hierarchies for Molecular functions, Biological processes and Cellular locations. The annotations can be used to identify functions that are enriched in the set, but this analysis can be misleading since the underlying distribution of genes among various functions is not uniform. For example, a large number of genes in a set might be kinases just because the genome contains many kinases. RESULTS: We use the Gene Ontology hierarchy and the annotations to pick significant functions and pathways by comparing the distribution of functions in a given gene list against the distribution of all the genes in the genome, using the hypergeometric distribution to assign probabilities. GObar is a web-based visualizer that implements this algorithm. The public website for GObar 2 can analyse gene lists from the yeast (S. cervisiae), fly (D. Melanogaster), mouse (M. musculus) and human (H. sapiens) genomes. It also allows visualization of the GO tree, as well as placement of a single gene on the GO hierarchy. We analyse a gene list from a genomic study of pre-mRNA splicing to demonstrate the utility of GObar. CONCLUSION: GObar is freely available as a web-based tool at http://katahdin.cshl.org:9331/GO2 and can help analyze and visualize gene lists from genomic analyses.

Algorithms↗

The value of fast and ultrafast T2-weighted MR imaging sequences in hepatic enhancement with ferumoxides: comparison with conventional spin-echo sequence.

PURPOSE: The efficacy of superparamagnetic iron oxide (SPIO) was evaluated with fast T2-weighted imaging sequences such as turbo spin-echo (TSE), half-Fourier single shot turbo spin echo (HASTE), and echo-planar imaging (EPI) in comparison with the conventional spin-echo (SE) sequence on a 1.5 Tesla MR unit. MATERIALS AND METHODS: In a phantom study, we prepared vials containing different concentrations of ferumoxides (0, 0.25, 0.5, 0.75, and 1 micromol Fe) in 2% agarose simulating the liver. In an animal study, contrast medium in doses of 10, 20, and 30 micromol/kg of ferumoxides was injected into the ear vein of rabbits weighing 3.0-4.0 kg under general anesthesia. MR imaging of the phantom and liver of the rabbits was obtained with the T2-weighted SE sequence (TR/TE=2000/20, 80), TSE sequences (TR/effective TE=2000/90, echo train length=7), HASTE (effective TE=64, 90 msec), and EPI (effective TE=64, 90 msec). Three rabbits in each group were imaged before and 1 hour after ferumoxides administration for in-vivo study. The Signal intensity of pre- and postcontrast imaging of the phantom or rabbits' livers was measured with operator-defined regions of interest, and signal-to-noise ratios (SNR) were obtained. Immediately after imaging, the rabbits were sacrificed and the livers were removed at autopsy, followed by ex-vivo study. In a clinical study, 10 micromol/kg of ferumoxides was given in 34 consecutive patients with 31 solid tumors. The liver SNR were evaluated for all 34 patients, and tumor to-liver contrast-to-noise ratios (CNR) were evaluated for all 31 solid lesions. The same series of imaging techniques as in the experimental studies was performed for quantitative and qualitative analyses. RESULTS: In both in-vitro and in-vivo studies, SNR of the phantom or rabbits' livers significantly decreased after ferumoxides administration. The decrease in SNR on excised rabbits' livers was 72% for EPI, 36% for HASTE, 61% for SE, and 51% for TSE at a dose of 10 micromol/kg of ferumoxides. In the clinical study, HASTE and TSE showed significant improvement in CNRs after ferumoxides administration (p<0.05). Visual analysis revealed improvement in tumor detection for all sequences. On EPI, although contrast was excellent, severe image distortion was seen. Although the signal decrease with HASTE and TSE was somewhat inferior to those with EPI and SE, respectively, the effect of contrast enhancement on HASTE and TSE was marked on visual analysis. CONCLUSION: Although TSE sequences and HASTE sequences are less susceptible to magnetic field inhomogeneities than SE and EPI sequences, the decrease in liver signal on HASTE and TSE sequences was comparable to that on EPI and SE sequences, respectively. These sequences are useful clinically for ferumoxides imaging, because they are less sensitive to motion artifacts.

Adult↗

Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma.

UNLABELLED: Conventional imaging techniques have serious limitations in the detection, staging, and restaging of prostate carcinoma. Anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC)is a synthetic l-leucine analog that has excellent in vitro uptake within the DU-145 prostate carcinoma cell line and orthotopically implanted prostate tumor in nude rats. There is little renal excretion compared with (18)F-FDG. The present study examines anti-(18)F-FACBC uptake in patients with newly diagnosed and recurrent prostate carcinoma. METHODS: Fifteen patients with a recent diagnosis of prostate carcinoma (n = 9) or suspected recurrence (n = 6) underwent 65-min dynamic PET/CT of the pelvis after intravenous injection of 300-410 MBq anti-(18)F-FACBC followed by static body images. Each study was evaluated qualitatively and quantitatively. Maximum standardized uptake values were recorded in the prostate or prostate bed, and within lymph nodes at 4.5 min (early) and 20 min (delayed), and correlated with clinical, imaging and pathologic follow-up. Time-activity curves were also generated for benign and malignant tissue. RESULTS: In the 8 patients with newly diagnosed prostate carcinoma who underwent dynamic scanning, visual analysis correctly identified the presence or absence of focal neoplastic involvement in 40 of 48 prostate sextants. Pelvic nodal status correlated with anti-(18)F-FACBC findings in 7 of 9 patients and was indeterminate in 2 of 9. In all 4 patients in whom there was proven recurrence, visual analysis was successful in identifying disease (1 prostate bed, 3 extraprostatic). In 3 of these patients, (111)In-capromab-pendetide had no significant uptake at nodal and skeletal foci. Malignant lymph node uptake in both the staging and restaging patients was significantly higher than benign nodal uptake. Though uptake faded with time, in all 6 patients with either lymph node metastases or recurrent prostate bed carcinoma, there was intense persistent uptake at 65 min. CONCLUSION: Anti-(18)F-FACBC is a promising radiotracer for imaging prostate carcinoma. Radiotracer uptake was demonstrated in primary and metastatic disease. Future research should investigate the mechanism of radiotracer uptake in normal and pathologic tissue and develop a clinical imaging strategy for initial staging and restaging.

Aged↗

Online-delivered eye movement desensitization and reprocessing treatment for adults with post-traumatic stress disorder due to multiple traumas: a non-concurrent multiple baseline design.

Background: No controlled studies incorporating randomization have been conducted to investigate the effectiveness of online eye movement desensitization and reprocessing (EMDR) treatment, despite its use in clinical practice.Objective: This study evaluated the effect of online EMDR treatment in adults aged 18-65&#xa0;years with post-traumatic stress disorder (PTSD) resulting from multiple traumas.Method: A multiple baseline single-case experimental design (n&#x2009;=&#x2009;21) was employed. Participants were patients with PTSD due to multiple traumas, recruited from a mental healthcare institution in the Netherlands. They were randomly assigned to baseline phases of 2, 3.5, or 5.5 weeks. After this, participants received 10 weekly online EMDR sessions. The primary outcome was the total score on an adapted version of the PTSD Checklist for DSM-5 (PCL-5), which was administered twice a week during baseline and intervention phases, and once 12 weeks after the end of the intervention phase. We performed visual analysis and calculated the improvement rate difference (IRD) for each individual separately to determine whether online EMDR was effective. We also performed a paired t-test and calculated Cohen's d for pretreatment and post-treatment comparisons, and pretreatment versus follow-up to evaluate effects at the group level.Results: Visual analysis and IRD scores showed that the treatment was effective for 15 participants, with effect sizes ranging from small to very large. The mean scores on the PCL-5 at group level decreased significantly over time between pretreatment and post-treatment (Mdiff&#x2009;=&#x2009;23.6, Cohen's d&#x2009;=&#x2009;1.34, 95% CI 0.74-1.93), as well as between pretreatment and follow-up (Mdiff&#x2009;=&#x2009;27.2, Cohen's d&#x2009;=&#x2009;1.62, 95% CI 0.95-2.27).Conclusion: Most participants showed a reduction in symptoms following the start of the online EMDR. Furthermore, at the group level there was a significant and clinically relevant reduction in symptoms over time. This provides preliminary evidence for the effectiveness of online EMDR treatment.

Humans↗

Parieto-occipital areas involved in efficient filtering in search: a time course analysis of visual marking using behavioural and functional imaging procedures.

Search for a colour-form conjunction target can be facilitated by presenting one set of distractors prior to the second set of distractors and the target: the preview benefit (Watson & Humphreys, 1997). The early presentation of one set of distractors enables them to be efficiently filtered from search. We report two studies investigating the time course of the preview benefit. In Experiment 1 we use a standard reaction time analysis to show that the benefit has a relatively slow time course; old items need to precede the new set by 600 ms or more in order to be fully filtered from search. Furthermore, the reductions in reaction time across time in the preview condition varied nonlinearly with the display size, suggesting that old items were discounted from search in parallel. In Experiment 2 we examined the neural locus of this filtering effect over time, using positron emission tomography (PET). We show that regions of parieto-occipital cortex are selectively activated in a preview search condition relative to a detection baseline. These regions also increase in activation as the preview interval increases (and search then becomes easier), consistent with them modulating the parallel filtering of distractors from targets in spatial search. Interestingly, the same areas as those activated in preview search were also active in conjunction search relative to its own detection baseline. Thus these regions either modulate parallel filtering in conjunction search too, or they modulate different behavioural functions according to task constraints.

Adult↗

[Usefulness of the new imaging techniques, second harmonic and contrast in endocardial border visualization. Reliability analysis in segmental contraction assessment].

AIM: This study sought to determine if newer techniques significantly improve endocardial border definition in suboptimal acoustic windows, and the reproducibility of the evaluation of wall motion abnormalities according to the different techniques and degrees of expertise. METHODS: We studied a total of 20 consecutive patients with poor ultrasound window, to assess, if the use of tissue harmonic imaging (2H) or contrast with second harmonic (Levovist ; 4 g i.v.), (2HC) improves endocardial border visualization. In order to analyze inter and intraobserver reliability with the different techniques, four observers with different degrees of expertise were each asked to assess the segmental wall motion score of 31 consecutive echocardiograms. RESULTS: The quality of the image was clearly superior with 2H and 2HC compared with 2D. This difference was larger in apex and lateral endocardial border from 0.9 and 1 to 1.5 and 1.64 (p < 0.001) with 2H. 2HC was found to slightly but significantly improve the endocardial definition in apex compared with 2H (1.64 vs 1.81; p = 0.016). The percentage of segments assessed for interobserver variability significantly improve with 2H and 2HC (2D = 50%, 2H = 75% and 2HC = 95%). Interobserver agreement with the different techniques between the experienced observers did not statistically differ. The less experienced observer presented a significantly lower interobserver reliability than those with experience, and did not improve with 2H and 2HC. CONCLUSIONS: a) Native tissue harmonic imaging and second harmonic imaging with contrast (Levovist ) significantly improves endocardial border visualization; b) the newer imaging techniques significantly improve performance (percentage of evaluated segments) without decreasing reliability, and c) experience in assessing wall motion is the main factor in interobserver agreement.

Echocardiography↗

Cardiovascular magnetic resonance: myocardial perfusion.

There is growing evidence that the noninvasive assessment of myocardial perfusion with cardiovascular magnetic resonance is a valid and accurate tool for the assessment of ischemic heart disease and its introduction into routine clinical evaluation of patients is rapidly expected. Magnetic resonance measurements allow the evaluation of reversible and irreversible myocardial ischemia, the assessment of acute myocardial infarction, as well as the recognition and detection of viable myocardium. Magnetic resonance perfusion measurements are mainly performed with T1-shortening contrast agents such as gadolinium-DTPA either by visual analysis or based on the analyses of signal intensity time curves. For the detection of myocardial ischemia the first pass kinetics of a gadolinium-DTPA bolus and for the detection of myocardial necrosis and the definition of viable myocardium steady state distribution kinetics are assessed. Quantitative analysis of myocardial perfusion can be performed but requires complex modeling due to the characteristics of gadolinium-DTPA. Thus, semi-quantitative parameters are preferred. There is accumulating evidence in the literature that magnetic resonance imaging can be used for the detection of coronary artery stenosis with high diagnostic accuracy both with semi-quantitative or visual analysis. Myocardial infarction can be reliably detected and the infarcted area determined. Non-reperfused infarcted myocardium can be differentiated from reperfused myocardium by different enhancement patterns that correlates with viability. Cardiac magnetic resonance is a promising technique that can combine different functional studies during one examination, such as the assessment of wall motion and perfusion at rest and stress. With further improvements in analysis software magnetic resonance perfusion measurement may rapidly become a routine tool for the assessment of patients with coronary artery disease.

Contrast Media↗

Saccadic suppression precedes visual motion analysis.

There is now good evidence that perception of motion is strongly suppressed during saccades (rapid shifts of gaze), presumably to blunt the disturbing sense of motion that saccades would otherwise elicit. Other aspects of vision, such as contrast detection of high-frequency or equiluminant gratings, are virtually unaffected by saccades [1] [2] [3] [4] [5]. This has led to the suggestion that saccades may suppress selectively the magnocellular pathway (which is strongly implicated in motion perception), leaving the parvocellular pathway unaffected [5] [6]. Here, we investigate the neural level at which perception of motion is suppressed. We used a simple technique in which an impression of motion is generated from only two frames, allowing precise control over the stimulus [7] [8]. One frame has a certain fixed contrast, whereas the contrast of the other (the test frame) is varied to determine the threshold for motion discrimination (that is, the lowest test-frame contrast level at which the direction of motion can be correctly guessed). Contrast thresholds of the test depended strongly and non-monotonically on the contrast of the fixed-contrast frame, with a minimum at medium contrast. To study the effect of saccadic suppression, we triggered the two-frame sequence by a voluntary saccade. Thresholds during saccades increased in a way that suggested that saccadic suppression precedes motion analysis: when the test frame was first in the motion sequence there was a general depression of sensitivity, whereas when it was second, the contrast response curve was shifted to a higher contrast range, sometimes even resulting in higher sensitivity than without a saccade. The dependence on presentation order suggests that saccadic suppression occurs at an early stage of visual processing, on the single frames themselves rather than on the combined motion signal. As motion detection itself is thought to occur at an early stage, saccadic suppression must take place at a very early phenomenon.

Humans↗

The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis.

Malignant external otitis (MEO) is a severe infectious disorder usually caused by Pseudomonas aeruginosa, which most frequently affects diabetic patients. Due to its rarity, the diagnosis of MEO is often not made promptly. Extension into deeper structures or chronic osteomyelitis may occur without signs of infection on local clinical examination. Of the imaging techniques, magnetic resonance imaging provides a fairly adequate picture of the spread of the disease, but, as with computed tomography (CT) scanning and bone scintigraphy, the images remain unchanged for a long time after disease regression. The objective of this study was to establish whether quantitative gallium-67 single-photon emission tomography (SPET) represents an accurate method for the assessment of infection and, moreover, for the monitoring of therapeutic effect. Eight patients (five males, three females) with the clinical diagnosis of MEO were studied. In three patients antibiotic treatment was prolonged for several weeks because visual analysis of gallium scintigraphy still showed slightly increased uptake in the affected area on the first follow-up scan. In one patient, it was decided to stop antibiotic treatment despite a slight increase in uptake on the second follow-up scan. Lesion to non-lesion (L/NL) ratios obtained from 67Ga SPET images at initial diagnosis and during follow-up were assessed in correlation with clinical and biochemical data and with the results of CT scans. In addition to a raised erythrocyte sedimentation rate (ESR), all patients showed increased uptake on the affected side, with L/NL ratios ranging from 1.4 to 3.6 at the time of diagnosis. CT scans failed to demonstrate abnormalities in four patients. Including four scans demonstrating slightly increased uptake in the affected area, L/NL ratios after 6-8 weeks of antibiotic treatment were 1.0+/-0.1. Despite a persistently elevated ESR in the majority of patients, none of them demonstrated local recurrence or complications during follow-up. In all patients, leucocyte count was within the normal range throughout the course. No relation was found between the slightly increased uptake on the follow-up scans and surgical treatment. It is concluded that in addition to the visual analysis of 67Ga SPET imaging, L/NL ratios should be calculated for a more accurate assessment of disease activity in MEO. Despite visually slightly increased uptake, L/NL ratios of 1.0+/-0.1 during follow-up are highly indicative of complete recovery, regardless of ESR values or leucocytosis. CT scans are of little value for diagnosis or for monitoring of therapeutic effect.

Adolescent↗

Visualization and analysis of molecular scanner peptide mass spectra.

The molecular scanner combines protein separation using gel electrophoresis with peptide mass fingerprinting (PMF) techniques to identify proteins in a highly automated manner. Proteins separated in a 2-dimensional polyacrylamide gel (2-D PAGE) are digested in parallel and transferred onto a membrane keeping their relative positions. The membrane is then sprayed with a matrix and inserted into a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer, which measures a peptide mass fingerprint at each site on the scanned grid. First, visualization of PMF data allows surveying all fingerprints at once and provides very useful information on the presence of chemical noise. Chemical noise is shown to be a potential source for erroneous identifications and is therefore purged from the mass fingerprints. Then, the correlation between neighboring spectra is used to recalibrate the peptide masses. Finally, a method that clusters peptide masses according to the similarity of the spatial distributions of their signal intensities is presented. This method allows discarding many of the false positives that usually go along with PMF identifications and allows identifying many weakly expressed proteins present in the gel.

Algorithms↗

Cortical analysis of visual context.

Objects in our environment tend to be grouped in typical contexts. How does the human brain analyze such associations between visual objects and their specific context? We addressed this question in four functional neuroimaging experiments and revealed the cortical mechanisms that are uniquely activated when people recognize highly contextual objects (e.g., a traffic light). Our findings indicate that a region in the parahippocampal cortex and a region in the retrosplenial cortex together comprise a system that mediates both spatial and nonspatial contextual processing. Interestingly, each of these regions has been identified in the past with two functions: the processing of spatial information and episodic memory. Attributing contextual analysis to these two areas, instead, provides a framework for bridging between previous reports.

Adult↗

On some mathematical techniques for the analysis of visual spectral sensitivities.

Starting from known spectral properties of visual photopigments and photoreceptors, a mathematical construction of neural response functions to visual stimuli is obtained. Included in this is a somewhat general derivation of the univariance principle. Temporal dependence of response on stimulus is included in the formulation. Special attention is given to the case of flash stimuli and their resulting spectral sensitivities. This formulation is applied to certain physiological spectral sensitivity measurements that are at variance with known spectrophometric results. An analysis of the data in these cases suggests that they correspond to "pseudo-pigments" arising from the neural interaction of several photopigments. The method of analysis is constructive and identifies the gamma-max's of the interacting photopigments. These are found to be in good agreement with existing spectrophotometric measurements.

Animals↗

Magnetization transfer measurements of the hippocampus in patients with Alzheimer's disease, vascular dementia, and other types of dementia.

BACKGROUND AND PURPOSE: Although atrophy of structures in the medial temporal lobe has been considered an indication of Alzheimer's disease (AD), atrophic changes on MR images have also been associated with other dementing diseases and are not specific to AD. This study was undertaken to determine whether characteristic alterations in the hippocampus of patients with AD are detectable with magnetization transfer (MT) imaging. METHODS: Coronal MT imaging was performed in 35 patients with probable AD, in 14 patients with vascular dementia, in 13 patients with other types of dementia, and in 23 control subjects to measure MT ratios of the hippocampus. Medial temporal lobe atrophy was graded subjectively on a five-point scale. RESULTS: Scores of medial temporal lobe atrophy in all dementia groups were significantly higher than those in control subjects, but no differences were found among the dementia groups. MT ratios in the hippocampus were significantly lower in patients with AD than in those with non-AD dementia and in the control subjects; however, no differences were found between the non-AD dementia patients and the control subjects. MT ratio measurements were better than visual analysis of atrophy for differentiating AD patients from those with non-AD dementia (an overall discrimination rate of 77% versus 65%). MT ratios significantly correlated with scores on the Mini-Mental State Examination and with medial temporal lobe atrophy in AD patients but not in patients with non-AD dementia. CONCLUSION: MT measurements may be more specific than visual analysis in detecting structural damage of the hippocampus in AD patients and might be useful in discriminating AD from vascular dementia and other types of dementia.

Aged↗

Myocardial viability assessment with technetium-99m-tetrofosmin and thallium-201 reinjection in coronary artery disease.

UNLABELLED: Exercise-rest 99mTc-tetrofosmin myocardial perfusion images with a 2-day protocol was compared to exercise-redistribution-reinjection 201Tl images to assess the ability of 99mTc-tetrofosmin to detect viable myocardium. METHODS: We studied 25 patients with coronary artery disease and regional or global left ventricular dysfunction. Myocardial SPECT images with 99mTc-tetrofosmin were obtained 10 min after injection during exercise and 1 and 3 hr after rest injection. Within 1 wk of the 99mTc-tetrofosmin study, exercise-redistribution-reinjection 201Tl SPECT imaging was performed. RESULTS: Visual analysis demonstrated concordance between 201Tl and 99mTc-tetrofosmin imaging for defect reversibility in 126 of 209 segments (60%), with initial defects on both exercise 201Tl and 99mTc-tetrofosmin images. In the remaining discordant 83 segments (40%), 73 (88%) appeared nonreversible on 99mTc-tetrofosmin imaging but were reversible on 201Tl imaging. CONCLUSION: On the basis of defect reversibility by visual analysis, exercise-rest 99mTc-tetrofosmin imaging underestimates myocardial viability compared to 201Tl reinjection imaging. The identification of viable myocardium with both 99mTc-tetrofosmin and 201Tl can be greatly enhanced to a similar degree if the severity of reduction in activity within nonreversible defects is considered. These two agents may provide comparable information about myocardial viability by quantitative analysis of defect severity.

Coronary Disease↗

[Visual pattern analysis and reasoning: Ravens' Coloured Progressive Matrices in old-age and very-old-age adults].

Sixty-five non-demented elderly adults, born between 1895 and 1918 (mean age +/- sd: 80.0 +/- 5.4) were tested with Raven's Coloured Progressive Matrices (CPM). Subjects were recruited from homes for the aged and were rated by the staff as free from any symptoms of dementia or other psychiatric disease. Mean number of years of education was 8.2 (range 5 to 18). CPM scores ranged from 9 to 35 with mean +/- sd of 25.9 +/- 5.9. Subjects who had received more formal education performed better on the CPM (Pearson's r: 0.49). When education was controlled for in the analysis, the correlation between age and performance was attenuated and did not reach statistical significance (Pearson's r: -0.24). Test results appeared to be specific for generations, regardless of age. Mean performance in this sample was significantly higher than less recently published norms suggest. Analysis of item content revealed that the CPM consists of three main types of problems: two of a predominantly visuospatial type (12 items of simple continuous pattern-completion and 15 concrete items showing progressive changes in one or two directions) and 9 items of an abstract reasoning type. The concrete visuospatial items appear very useful in the assessment of visuoperceptive dysfunction, as for example in visual apperceptive agnosia. The abstract matrices were very difficult for most of our elderly subjects, so that these items cannot be used to detect deviations from normal old age.

Aged↗

Validation of a simple technique for the detection of abnormal mucosal cell replication in humans.

Abnormal intestinal crypt cell proliferation is considered to be an important early risk marker for colorectal cancer but measurement of the rate and spatial distribution of cell division by histochemical localization of DNA synthesis is labour-intensive and expensive. We developed and evaluated a simpler technique for measurement of these parameters using direct visual analysis of mitotic figures in microdissected crypts. The direct crypt analysis technique was applied to colorectal biopsies from patients with ulcerative colitis or no mucosal abnormality. A characteristic shift of cell division toward the intestinal lumen was detected in patients with ulcerative colitis. The direct method was validated using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell proliferation. The crypt cell proliferation rate (CCPR) was measured by the metaphase-arrest technique and the results were compared with direct crypt analysis. There was a fivefold range of CCPR values at three sampling sites across the dietary groups. An excellent linear correlation between the results by the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the spatial distribution of dividing cells between five zones in colonic crypts, determined by the new method or by staining with BrdU, was compared. Good agreement was again achieved. Visual analysis of intact crypts is a valid technique for the measurement of crypt cell cytokinetics and it is particularly suited for use in a clinical environment.

Animals↗